The present invention is directed to peptide pharmaceutical compositions and uses thereof, in particular, small peptides including the amino acid sequence, Glx-Lys. These peptide compositions are useful for modulation of the immune system; the treatment of immunodepressed states and of opportunistic infections in immunodepressed states associated with acquired immune deficiency syndrome; treatment of infections caused by bacterial, viral, fungal, and parasitic organisms; augmentation of vaccination response; treatment of atopic states, treatment of anemias; treatment of leukocytic disorders; and the like.
A wide variety diseases are caused by abnormalities of the immune system and hematological systems of animals including man. Further, the immune system is required to treat many other diseases. For example, immunodeficiencies such as the acquired immunodeficiency syndrome (AIDS) most commonly cause premature death and disability by making the person susceptible to infections and malignancies. This susceptibility is caused by a weakening of the immune system. Specifically, the HIV virus that causes AIDS attacks and kills T helper cells. Loss of T helper cells compromises the host""s ability to fight infections by normal immunological mechanisms. Many types of malignancy are also associated with immunodeficient states suggesting that they are caused by a failure of normal host immune surveillance systems. Many diseases cause secondary immunodeficiency allowing for more rapid progression of the primary disease or the development of secondary diseases. Methods to enhance suppressed immune systems have not achieved high levels of efficacy.
Diseases may also be caused by hyperactivity of the immune system. For example, collagen vascular diseases are associated with immunologically-mediated damage to the host tissue. Such diseases include multiple sclerosis, rheumatoid arthritis and the like. These diseases afflict many individuals and cause significant morbidity and mortality. Treatments generally include immune suppression. Unfortunately, generalized immune suppression often results in increased incidence of infections and malignancies. Therefore, to treat one disease patients are placed at risk for developing other, possibly life threatening, diseases.
Immunological stimulation, even in healthy individuals, may aid in the treatment of several diseases. Infectious diseases may be more effectively treated by stimulation of the immune system. The enhanced immunological response may work with other treatments to eliminate the infection more readily. Also, specific immune stimulation has been shown to reduce tumor size in some malignancies. Also, many drugs used for primary treatment of infections and malignancies have significant side effects. Therefore, it is desirable to reduce the dose of the primary drug whenever possible.
What is needed in the art are compositions and methods for modulating the immune system. Ideally, these compounds and methods would be able to stimulate suppressed or deficient immune systems as well as reduce immune hyperactivity. Also these compounds and methods should act to restore a natural balance to the immune system. Quite surprisingly, the present invention fulfills these and other related needs.
The present invention provides compositions comprising a peptide having the formula Rxe2x80x2-Glx-Glx-Lys-Rxe2x80x3 (SEQ ID NO:1) or a pharmaceutically acceptable salt thereof; wherein Glx is Glu or Gln; Rxe2x80x2 is H- or a first amino acid sequence having fewer than 7 amino acids; Rxe2x80x3 is -H or a second amino acid sequence having fewer than 7 amino acids; and the peptide has a sequence of at least 5 and not more than 9 amino acids. Generally, Rxe2x80x2 is H-, Thr-Ala-, Thr-Pro-, Ser-Ala-, Ser-Pro-, Ser-Ser-, Met-Leu-Thr-Ala- (SEQ ID NO:32), or Leu-Thr-Ala-; and Rxe2x80x3 is -H, -Ala, -Ala-Ala or -Ala-Val (SEQ ID NOS:2-31). In preferred embodiments, the peptide is L-Thr-L-Pro-L-Glu-L-Glu-L-Lys (SEQ ID NO:33) or L-Thr-L-Ala-L-Glu-L-Glu-L-Lys (SEQ ID NO:34).
Also provided are pharmaceutical preparations comprising a peptide having the formula Rxe2x80x2-Glx-Lys-Rxe2x80x3 (SEQ ID NO:35) or a pharmaceutically acceptable salt thereof, wherein Glx is Glu or Gln; Rxe2x80x2 is H- or a first amino acid sequence having fewer than 7 amino acids; Rxe2x80x3 is -H or a second amino acid sequence having fewer than 7 amino acids; and the peptide has a sequence of at least 2 and not more than 9 amino acids; and a physiologically acceptable carrier. In preferred embodiments, the peptide is L-Glu-L-Lys, L-Thr-L-Ala-L-Glu-L-Glu-L-Lys (SEQ ID NO:34) or L-Thr-L-Pro-L-Glu-L-Glu-L-Lys (SEQ ID NO:33).
Methods for using the peptides of the present invention are also provided. These methods include administration of the pharmaceutical preparations of the present invention for immunomodulation of a host""s immune system, treatment of infections, treatment of anemias, treatment of atopic states, and treatment of leukocytic disorders.